Studies of the administration of testosterone and estradiol to normal men at physiological dosage demonstrate that estradiol, which is produced primarily by peripheral conversion of testosterone, accounts for the majority of the suppressive effects of testosterone of LH and FSH secretion. Blockade of estradiol action, by use of the antiestrogen, clomiphene, completely reverses the suppressive effects of testosterone on plasma gonadotropin concentrations. In addition, administration of testolactone, a drug which blocks the peripheral conversion of testosterone to estradiol, increases both LH and FSH serum levels significantly. These data emphasize the important role of peripheral aromatization of testosterone in its physiological interaction in the hypothalamus and pituitary. It is now evident that in men with profound testicular failure or who are functionally castrated gonadotropin concentrations are suppressable following testosterone administration and are unresponsive to suppression by pure androgens but retain response to estrogenic component of testosterone by its peripheral conversion.